LYW-6, a novel cryptotanshinone derived STAT3 targeting inhibitor, suppresses colorectal cancer growth and metastasis

Wang, Huan; Zhe, Liu; Guan, Lingnan; Li, Jiankang; Chen, Siyi; Yu, Wenying; Lai, Maode

doi:10.1016/j.phrs.2020.104661

Cited by 17 publications

(13 citation statements)

References 27 publications

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“…By inhibition of STAT3, CT suppresses drug resistance and enhances anti‐tumor activity of chemotherapeutic agents such as paclitaxel (Dong et al, 2018; Wang et al, 2017). It is worth mentioning that derivatives of CT such as LYW‐6 are also able to inhibit cancer growth via STAT3 down‐regulation (Wang et al, 2020). These studies are in agreement with the fact that STAT3 is one of the major targets of CT and its derivatives in cancer therapy.…”

Section: Cryptotanshinone As a Modulator Of Molecular Pathways In Difmentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.

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Section: Cryptotanshinone As a Modulator Of Molecular Pathways In Difmentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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“…Although autophagy is well recognized as a cell survival process that promotes tumor development, it can also participate in programmed cell death independent of caspase (Rouschop et al, 2010;Denton and Kumar, 2019;Gómez-Díaz et al, 2019). In the current study, autophagy occurrence was detected in CRC cells treated with CPT (Park et al, 2014;Wang et al, 2020). Interestingly, autophagy inhibitor selectively prevented HCT116 cells death while have negative effects on SW620 cells.…”

Section: Discussionmentioning

confidence: 49%

“…It is generally accepted that the generation of endoplasmic reticulum stress plays an important role in apoptosis by changing the internal environment of cells (Alper et al, 2020) (Wu et al, 2020). Recent studies reported that CPT is a crucial ER stress promoter in some colorectal cancers (Wang L. et al, 2020). Therefore, the roles of endoplasmic reticulum stress in growth of HCT116 and SW620 were explored in the current study.…”

Section: Cryptotanshinone Monitored Hct116 Cells Apoptosis Mediated By Endoplasmic Reticulum Stress Which Was Lowly Expressed In Crc Tissmentioning

confidence: 99%

“…Herbs have recently aroused more and more interests in the discovery of anticancer therapies because they have long been used as alternative therapies for various diseases, including cancer, coronary heart disease, and diabetes, with relatively fewer side effects (Zhao et al, 2019;He et al, 2020;Sun et al, 2020;Zhao et al, 2020;Zheng et al, 2020). Multiple studies have reported that some active ingredients of Salvia miltiorrhiza Bunge (Danshen) have anti-tumor activities, including hepatoma, and prostatic cancer (Xu et al, 2012;Luo et al, 2020;Wang et al, 2020). Cryptotanshinone (CPT) is one important active ingredient from Danshen and is usually used to treat atherosclerosis, alzheimer's disease, hyperlipidemia, liver fibrosis, chronic renal failure, and gynecological diseases in Asian countries, with few reported serious side effects (Xu et al, 2012;Cai et al, 2016;Ding et al, 2016;Liu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy

Zhao

et al. 2021

Front. Pharmacol.

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Among cancers, colorectal cancer (CRC) has one of the highest annual incidence and death rates. Considering severe adverse reactions associated with classical chemotherapy medications, traditional Chinese medicines have become potential drug candidates. In the current study, the effects of cryptotanshinone (CPT), a major component of Salvia miltiorrhiza Bunge (Danshen) on CRC and underlying mechanism were explored. First of all, data from in vitro experiments and in vivo zebrafish models indicated that CPT selectively inhibited the growth and proliferation of HCT116 and SW620 cells while had little effect on SW480 cells. Secondly, both ER stress and autophagy were associated with CRC viability regulation. Interestingly, ER stress inhibitor and autophagy inhibitor merely alleviated cytotoxic effects on HCT116 cells in response to CPT stimulation, while have little effect on SW620 cells. The significance of apoptosis, autophagy and ER stress were verified by clinical data from CRC patients. In summary, the current study has revealed the anti-cancer effects of CPT in CRC by activating autophagy signaling mediated by ER stress. CPT is a promising drug candidate for CRC treatment.

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“…Previous studies have indicated a correlation between phosphorylated STAT3 (pSTAT3) and anti‐EGFR–based therapy in colon cancer (Dobi et al, 2013; Ung et al, 2014; Zhuang et al, 2019). According to the earlier reports, an abnormal increase of STAT3 activation has demonstrated to be connected with the elevated cell proliferation and invasion of colorectal cancer (H. Wang et al, 2020). As reported by Li et al, activation of STAT3/Bcl2/Bcl‐XL survival pathway due to erlotinib treatment showed to be in association with cancer cell resistance toward erlotinib.…”

Section: Discussionmentioning

confidence: 98%

Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinib‐resistant SW480 cell line

Asadi

Fathi

Rismani

et al. 2021

Cell Biology International

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Signal transducer and activator of transcription 3 (STAT3) is a critical regulator for angiogenesis, cell cycle progression, apoptosis, and drug resistance. Resistance toward EGF receptor (EGFR) inhibitors is a significant clinical concern for metastatic colon cancer patients. The present study aimed to evaluate the blocking influences of STAT3 decoy oligodeoxynucleotides (ODNs) on the STAT3 survival signaling pathway in nonresistant and erlotinib‐resistant SW480 colon cancer cells. First, STAT3 decoy and scramble ODNs were designed according to STAT3 elements in the promoter region of MYCT1 gene and tested for the interaction of STAT3 protein with designed ODNs via in silico molecular docking study. Then, the efficiency of transfection and subcellular localization of ODNs were assessed using flow cytometry and fluorescence microscopy, respectively. Cell viability, cell cycle, and apoptosis tests, scratch and colony formation assays, and real‐time PCR were also used to study the cancerous properties of cells. A considerable decrease in proliferation of colon cancer cells was observed with blockade of STAT3 signaling due to cell cycle arrest and induced apoptosis via downregulation of cyclin D1 and Bcl‐XL, respectively. Furthermore, upon transfecting STAT3 decoy ODNs, colony formation potential and migration activity in both SW480 colon cancer cell lines were decreased compared to the control groups. From this study, it could be concluded that STAT3 is critical for cell growth inhibition and metastatic properties reduction of resistant SW480 colon cancer cells; therefore, STAT3 decoy ODNs could be considered as potential therapeutics along with current remedies for treating drug‐resistant colon cancer.

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LYW-6, a novel cryptotanshinone derived STAT3 targeting inhibitor, suppresses colorectal cancer growth and metastasis

Cited by 17 publications

References 27 publications

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy

Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinib‐resistant SW480 cell line

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