tyb
noice dubs
next mabbe trim those previous down a couple of lines
o7
kek
Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth
https://www.frontiersin.org/articles/10.3389/fphar.2021.717529/full
Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth
www.frontiersin.orgShican Zhou‡, www.frontiersin.orgHang Wu‡, www.frontiersin.orgWenjuan Ning, www.frontiersin.orgXiao Wu, www.frontiersin.orgXiaoxiao Xu, www.frontiersin.orgYuanqiao Ma, www.frontiersin.orgXingwang Li, www.frontiersin.orgJunhong Hu†§, www.frontiersin.orgChenyu Wang§ and www.frontiersin.orgJunpeng Wang§
Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.
Introduction
Colorectal cancer (CRC) refers to malignant tumors in the ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and is one of the most common malignant tumors worldwide. Among all malignant tumors globally, CRC ranks third in incidence and second in mortality (Siegel et al., 2020). CRC has caused a heavy economic burden on the country and individuals (Maida et al., 2017). At present, the treatment of CRC mainly adopts a comprehensive treatment based on surgery, combined with radiotherapy, chemotherapy, targeted therapy, and other treatments (Modest et al., 2019). However, due to the complicated mechanism of the occurrence, development, and metastasis of CRC, there is still a lack of specific drugs for CRC treatment.
Ivermectin is a derivative of the 16-membered macrolide compound abamectin, which was first widely used in clinical practice as an antiparasitic drug (Laing et al., 2017). Ivermectin can increase the activity of γ-aminobutyric acid receptor or glutamate-chloride ion channel (Glu-Cl), increase the influx of chloride ions, and cause the cell membrane hyperpolarization, thereby blocking signal transmission between neurons and muscles (Martin et al., 2021), which exerts its antiparasitic effects. Ivermectin could be used, in addition to as an antiparasitic drug, as antiviral agents such as Flavivirus, HIV-1 virus, and SARS-CoV-2 virus (Mastrangelo et al., 2012; Wagstaff et al., 2012; Caly et al., 2020). Moreover, studies have shown that ivermectin has an inhibitory effect on various tumor cells and may be a potential broad-spectrum antitumor drug (Juarez et al., 2020). Juarez et al. (2020) have demonstrated that ivermectin is the most sensitive to breast cancer cells MDA-MB-231, MDA-MB-468, MCF-7, and ovarian SKOV-3; whereas ivermectin is the most nonsensitive to the prostate cancer cell line DU145. The induction of cell cycle arrest at G0/G1 mediates this effect of ivermectin on these sensitive cancer cells. Furthermore, ivermectin can inhibit the proliferation of cancer cells through p21-activated kinase 1 (PAK1)-induced autophagy, Caspase-dependent apoptosis, or immunogenic cell death regulate the signal pathways, including Hippo, Akt/mTOR, and WNT-TCF pathways to inhibit cancer cell proliferation (Liu et al., 2020). As known, ROS plays a vital role in the apoptosis caused by oxidative stress. ROS is a by-product of normal mitochondrial respiration. Stimuli such as infection, drought, cold, and ultraviolet light result in increased ROS in cells. Then, accumulative ROS could induce cells mitochondrial dysfunction and promote apoptosis in cells (Sinha et al., 2013). Evidence has shown that ivermectin-induced apoptosis is closely related to the production of ROS. Currently, there are few reports on the research of ivermectin in colorectal cancer.
Furthermore, new use of old drugs (that is, drug relocation) is a strategy for expanding old drugs and developing new uses, which has the advantages of low research and development cost and short development time (Pushpakom et al., 2019). Research on drug relocation of ivermectin is a shortcut to developing new antitumor drugs. Given this, we designed a study to explore the impact of ivermectin on the proliferation and apoptosis of CRC cells and the underlying mechanism.
kek
@350
#22096 >>18030455
>>18030499, >>18030502, >>18030518, >>18030540, >>18030548, >>18030687, >>18030699 moar ivermectin articles/studies
>>18030509 More Wisconsin voter fraud posts
>>18030512 Zelenskyy, BlackRock CEO Fink agree to coordinate Ukraine investment
>>18030516 Desperate flailing to excuse censorship
>>18030533 anons fav pol, dancin
>>18030536, >>18030543, >>18030573, >>18030601 Donald Trump failed to secure our border AND our elections. Change my mind.
>>18030542 Of course Gorsuch dissented and joined liberals on title 42/ title 42 voted to stay in effect
>>18030554, >>18030785 Refesher on pols and lies/potatus Biden
>>18030574 Is Zelensky missing?
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>>18030634, >>18030739, >>18030778 Refresher: 16 year plan: knowingly
>>18030640, >>18030641 White pill thread 26 posts. Marc Andreessen @pmarca
>>18030648 The Nuge: oil to fuel America for the next 200 years
>>18030651 Lake appeal filed
>>18030656 PF CONUS Activity
>>18030665 @MarioNawfal #FauciFiles - The Great Covid Debate w/ Star Panel
>>18030666 ebil trips of truth for the Green New Deal
>>18030669, >>18030715 President Trump Welcomes AndrewBrunsonto the White House
>>18030691 NAR: Pending Home Sales Decreased 4.0% in November, Year-over-year Down 37.8% (second lowest in history for index)
>>18030729 Alameda wallets become active days after SBF bail, community mulls foul play
>>18030735 2013-14 Ukrainian MP fakes ‘victim’ of Russian strike
>>18030741 Mom Blocked from Taking Daughter to Radio City Music Hall Event as Result of Facial Recognition and Blacklist
>>18030743 Utah junior high staff member arrested
>>18030744, >>18030751 Lavrov Says Pentagon Threatening To Assassinate Putin
>>18030753 Message from Watkins: This coming January 6 will mark two years of imprisonment without trial for many of The United States of America’s prisoners of war
>>18030754 Air Force scraps spy planes used to fight border drug war
>>18030761 Ukrainian Law Firm Uses Stasi Tactics to ‘Cleanse’ Europe of Suspected ‘Russians’
>>18030784 "Tired of the Apologies": Workers, Flyers Say Southwest Airlines Meltdown Was Decades in the Making
>>18030802, >>18030811, >>18030827 Zelensky Says Ukraine Ready to Join WEF Meeting in Davos as It Seeks Postwar Funding
>>18030806 Fmr. DNI Ratcliffe: I Confirmed Hunter Laptop Was Legitimate in 2020, But There Was ‘a Disinformation Campaign on Behalf of Joe Biden’
>>18030820 Glasgow Sex Trafficker Jagpal Singh was BBC Reality News Show Star
>>18030835 Global Geoengineering Death Agenda Exposed Before The New World Order!
top fucken kek
60's
@500
#22096 >>18030455
>>18030499, >>18030502, >>18030518, >>18030540, >>18030548, >>18030687, >>18030699 moar ivermectin articles/studies
>>18030509 More Wisconsin voter fraud posts
>>18030512 Zelenskyy, BlackRock CEO Fink agree to coordinate Ukraine investment
>>18030516 Desperate flailing to excuse censorship
>>18030533 anons fav pol, dancin
>>18030536, >>18030543, >>18030573, >>18030601 Donald Trump failed to secure our border AND our elections. Change my mind.
>>18030542 Of course Gorsuch dissented and joined liberals on title 42/ title 42 voted to stay in effect
>>18030554, >>18030785 Refesher on pols and lies/potatus Biden
>>18030574 Is Zelensky missing?
>>18030593, >>18030571 The Bee: Spelling bee contestant asks the definition of woman
>>18030620, >>18030717 Gold Warriors : How America Secretly Recovered Yamashita's/Japanese Imperial Family Gold
>>18030634, >>18030739, >>18030778 Refresher: 16 year plan: knowingly
>>18030640, >>18030641 White pill thread 26 posts. Marc Andreessen @pmarca
>>18030648 The Nuge: oil to fuel America for the next 200 years
>>18030651 Lake appeal filed
>>18030656 PF CONUS Activity
>>18030665 @MarioNawfal #FauciFiles - The Great Covid Debate w/ Star Panel
>>18030666 ebil trips of truth for the Green New Deal
>>18030669, >>18030715 President Trump Welcomes AndrewBrunsonto the White House
>>18030691 NAR: Pending Home Sales Decreased 4.0% in November, Year-over-year Down 37.8% (second lowest in history for index)
>>18030729 Alameda wallets become active days after SBF bail, community mulls foul play
>>18030735 2013-14 Ukrainian MP fakes ‘victim’ of Russian strike
>>18030741 Mom Blocked from Taking Daughter to Radio City Music Hall Event as Result of Facial Recognition and Blacklist
>>18030743 Utah junior high staff member arrested
>>18030744, >>18030751 Lavrov Says Pentagon Threatening To Assassinate Putin
>>18030753 Message from Watkins: This coming January 6 will mark two years of imprisonment without trial for many of The United States of America’s prisoners of war
>>18030754 Air Force scraps spy planes used to fight border drug war
>>18030761, >>18030897 Ukrainian Law Firm Uses Stasi Tactics to ‘Cleanse’ Europe of Suspected ‘Russians’
>>18030784 "Tired of the Apologies": Workers, Flyers Say Southwest Airlines Meltdown Was Decades in the Making
>>18030802, >>18030811, >>18030827 Zelensky Says Ukraine Ready to Join WEF Meeting in Davos as It Seeks Postwar Funding
>>18030806 Fmr. DNI Ratcliffe: I Confirmed Hunter Laptop Was Legitimate in 2020, But There Was ‘a Disinformation Campaign on Behalf of Joe Biden’
>>18030820 Glasgow Sex Trafficker Jagpal Singh was BBC Reality News Show Star
>>18030835, >>18030915 Global Geoengineering Death Agenda Exposed Before The New World Order!
>>18030892 Israel helps Ukraine whitewash its Nazis
>>18030913 Former Google CEO Eric Schmidt is helping to fund the salaries of dozens of Biden officials
>>18030975 The Government lets slip a Tragic & Sinister Secret: COVID Vaccination is killing Thousands & is more dangerous than the Disease itself
>>18030978, >>18030996 Another Ukrainian terrorist attack foiled
>>18030992 @BernardKerik as he ANNIHILATES The January 6th Committee over their FAKE NEWS, LIES and Treachery. He Nails them for IGNORNING Ashli Babbitt
Last Call
#22096 >>18030455
>>18030499, >>18030502, >>18030518, >>18030540, >>18030548, >>18030687, >>18030699 moar ivermectin articles/studies
>>18030509 More Wisconsin voter fraud posts
>>18030512 Zelenskyy, BlackRock CEO Fink agree to coordinate Ukraine investment
>>18030516 Desperate flailing to excuse censorship
>>18030533 anons fav pol, dancin
>>18030536, >>18030543, >>18030573, >>18030601 Donald Trump failed to secure our border AND our elections. Change my mind.
>>18030542 Of course Gorsuch dissented and joined liberals on title 42/ title 42 voted to stay in effect
>>18030554, >>18030785 Refesher on pols and lies/potatus Biden
>>18030574 Is Zelensky missing?
>>18030593, >>18030571 The Bee: Spelling bee contestant asks the definition of woman
>>18030620, >>18030717 Gold Warriors : How America Secretly Recovered Yamashita's/Japanese Imperial Family Gold
>>18030634, >>18030739, >>18030778 Refresher: 16 year plan: knowingly
>>18030640, >>18030641 White pill thread 26 posts. Marc Andreessen @pmarca
>>18030648 The Nuge: oil to fuel America for the next 200 years
>>18030651 Lake appeal filed
>>18030656 PF CONUS Activity
>>18030665 @MarioNawfal #FauciFiles - The Great Covid Debate w/ Star Panel
>>18030666 ebil trips of truth for the Green New Deal
>>18030669, >>18030715 President Trump Welcomes AndrewBrunsonto the White House
>>18030691 NAR: Pending Home Sales Decreased 4.0% in November, Year-over-year Down 37.8% (second lowest in history for index)
>>18030729 Alameda wallets become active days after SBF bail, community mulls foul play
>>18030735 2013-14 Ukrainian MP fakes ‘victim’ of Russian strike
>>18030741 Mom Blocked from Taking Daughter to Radio City Music Hall Event as Result of Facial Recognition and Blacklist
>>18030743 Utah junior high staff member arrested
>>18030744, >>18030751 Lavrov Says Pentagon Threatening To Assassinate Putin
>>18030753 Message from Watkins: This coming January 6 will mark two years of imprisonment without trial for many of The United States of America’s prisoners of war
>>18030754 Air Force scraps spy planes used to fight border drug war
>>18030761, >>18030897 Ukrainian Law Firm Uses Stasi Tactics to ‘Cleanse’ Europe of Suspected ‘Russians’
>>18030784 "Tired of the Apologies": Workers, Flyers Say Southwest Airlines Meltdown Was Decades in the Making
>>18030802, >>18030811, >>18030827 Zelensky Says Ukraine Ready to Join WEF Meeting in Davos as It Seeks Postwar Funding
>>18030806 Fmr. DNI Ratcliffe: I Confirmed Hunter Laptop Was Legitimate in 2020, But There Was ‘a Disinformation Campaign on Behalf of Joe Biden’
>>18030820 Glasgow Sex Trafficker Jagpal Singh was BBC Reality News Show Star
>>18030835, >>18030915 Global Geoengineering Death Agenda Exposed Before The New World Order!
>>18030892 Israel helps Ukraine whitewash its Nazis
>>18030913 Former Google CEO Eric Schmidt is helping to fund the salaries of dozens of Biden officials
>>18030975 The Government lets slip a Tragic & Sinister Secret: COVID Vaccination is killing Thousands & is more dangerous than the Disease itself
>>18030978, >>18030996 Another Ukrainian terrorist attack foiled
>>18030992 @BernardKerik as he ANNIHILATES The January 6th Committee over their FAKE NEWS, LIES and Treachery. He Nails them for IGNORNING Ashli Babbitt
>>18031009 Number of Ukrainian refugees in Poland revealed
>>18031021 'Natural Right to the Land of Israel': Netanyahu Lays Out Far-reaching West Bank Settlement Plans
>>18031037 Non-sanctioned Russians unlikely to recover assets in EU – central bank
>>18031052 PF CONUS Update
>>18031061 Steve Cortes: Mass Amnesty Will Only Bury Blue Collar Workers
>>18031065 Biden Cabinet Member’s Major Conflict Of Interest, Dim inbreeding/nepotism
>>18031070 Mark Krikorian: Obama’s Border Policy Moderate Compared To Biden’s
>>18031098 Reminder: Fauci Argued Benefits of Gain-of-Function Research Outweighed Pandemic Risk in 2012 Paper
Final
#22096 >>18030455
>>18030499, >>18030502, >>18030518, >>18030540, >>18030548, >>18030687, >>18030699 moar ivermectin articles/studies
>>18030509 More Wisconsin voter fraud posts
>>18030512 Zelenskyy, BlackRock CEO Fink agree to coordinate Ukraine investment
>>18030516 Desperate flailing to excuse censorship
>>18030533 anons fav pol, dancin
>>18030536, >>18030543, >>18030573, >>18030601 Donald Trump failed to secure our border AND our elections. Change my mind.
>>18030542, >>18031128 Of course Gorsuch dissented and joined liberals on title 42/ title 42 voted to stay in effect
>>18030554, >>18030785 Refesher on pols and lies/potatus Biden
>>18030574 Is Zelensky missing?
>>18030593, >>18030571 The Bee: Spelling bee contestant asks the definition of woman
>>18030620, >>18030717 Gold Warriors : How America Secretly Recovered Yamashita's/Japanese Imperial Family Gold
>>18030634, >>18030739, >>18030778 Refresher: 16 year plan: knowingly
>>18030640, >>18030641 White pill thread 26 posts. Marc Andreessen @pmarca
>>18030648 The Nuge: oil to fuel America for the next 200 years
>>18030651 Lake appeal filed
>>18030656 PF CONUS Activity
>>18030665 @MarioNawfal #FauciFiles - The Great Covid Debate w/ Star Panel
>>18030666 ebil trips of truth for the Green New Deal
>>18030669, >>18030715 President Trump Welcomes AndrewBrunsonto the White House
>>18030691 NAR: Pending Home Sales Decreased 4.0% in November, Year-over-year Down 37.8% (second lowest in history for index)
>>18030729 Alameda wallets become active days after SBF bail, community mulls foul play
>>18030735 2013-14 Ukrainian MP fakes ‘victim’ of Russian strike
>>18030741 Mom Blocked from Taking Daughter to Radio City Music Hall Event as Result of Facial Recognition and Blacklist
>>18030743 Utah junior high staff member arrested
>>18030744, >>18030751 Lavrov Says Pentagon Threatening To Assassinate Putin
>>18030753 Message from Watkins: This coming January 6 will mark two years of imprisonment without trial for many of The United States of America’s prisoners of war
>>18030754 Air Force scraps spy planes used to fight border drug war
>>18030761, >>18030897 Ukrainian Law Firm Uses Stasi Tactics to ‘Cleanse’ Europe of Suspected ‘Russians’
>>18030784 "Tired of the Apologies": Workers, Flyers Say Southwest Airlines Meltdown Was Decades in the Making
>>18030802, >>18030811, >>18030827 Zelensky Says Ukraine Ready to Join WEF Meeting in Davos as It Seeks Postwar Funding
>>18030806 Fmr. DNI Ratcliffe: I Confirmed Hunter Laptop Was Legitimate in 2020, But There Was ‘a Disinformation Campaign on Behalf of Joe Biden’
>>18030820 Glasgow Sex Trafficker Jagpal Singh was BBC Reality News Show Star
>>18030835, >>18030915 Global Geoengineering Death Agenda Exposed Before The New World Order!
>>18030892 Israel helps Ukraine whitewash its Nazis
>>18030913 Former Google CEO Eric Schmidt is helping to fund the salaries of dozens of Biden officials
>>18030975 The Government lets slip a Tragic & Sinister Secret: COVID Vaccination is killing Thousands & is more dangerous than the Disease itself
>>18030978, >>18030996 Another Ukrainian terrorist attack foiled
>>18030992 @BernardKerik as he ANNIHILATES The January 6th Committee over their FAKE NEWS, LIES and Treachery. He Nails them for IGNORNING Ashli Babbitt
>>18031009 Number of Ukrainian refugees in Poland revealed
>>18031021 'Natural Right to the Land of Israel': Netanyahu Lays Out Far-reaching West Bank Settlement Plans
>>18031037 Non-sanctioned Russians unlikely to recover assets in EU – central bank
>>18031052 PF CONUS Update
>>18031061 Steve Cortes: Mass Amnesty Will Only Bury Blue Collar Workers
>>18031065 Biden Cabinet Member’s Major Conflict Of Interest, Dim inbreeding/nepotism
>>18031070 Mark Krikorian: Obama’s Border Policy Moderate Compared To Biden’s
>>18031098 Reminder: Fauci Argued Benefits of Gain-of-Function Research Outweighed Pandemic Risk in 2012 Paper
>>18031109 Today is National Pledge of Allegiance Day.
>>18031137 LCN Headlines 023 – Deja Vu Edition
#22096