Anti-Cancer Phytometabolites Targeting Cancer Stem Cells

Torquato, Heron Fernandes Vieira; Goettert, Márcia Inês; Justo, Giselle Z.; Paredes‐Gamero, Edgar Julian

doi:10.2174/1389202917666160803162309

Cited by 29 publications

(22 citation statements)

References 228 publications

(246 reference statements)

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“…Another vitamin E tocotrienol isomer, γ-TT, was reported to specifically target the CSC subpopulation in different cancer cells (colorectal, breast, prostate) 57 – 60 . This ability to counteract tumor growth by targeting both the bulk tumor cells and the CSC subpopulation has previously been reported for other natural compounds 21 – 25 .…”

Section: Discussionsupporting

confidence: 74%

“…Based on their key role in the mechanisms of drug resistance, CSCs are now considered a promising effective target for novel therapeutic strategies for cancer 11 , 12 . So far, several compounds, both synthetic and natural, have been reported to exert a significant antitumor activity by targeting cancer ‘stemness’, besides decreasing the viability of the bulk population of cells, in different types of tumors 25 , 47 .…”

Section: Discussionmentioning

confidence: 99%

“…So far, different therapeutic approaches specifically targeting the CSCs subpopulation have been developed for different types of tumors 18 , 19 , including melanoma 20 . Interestingly, natural compounds previously shown to possess anticancer activity were also reported to specifically target CSCs 21 – 25 .…”

Section: Introductionmentioning

confidence: 99%

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Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol

Marzagalli

Moretti

Messi

et al. 2018

Sci Rep

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The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture. Based on these data, we investigated whether δ-TT might target melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor activity of δ-TT are completely devoid of the ability to form melanospheres. In contrast, cells that escaped vemurafenib treatment show a higher ability to form melanospheres than control cells. δ-TT also induced disaggregation of A375 melanospheres and reduced the spheroidogenic ability of sphere-derived cells, reducing the expression of the ABCG2 marker. These data demonstrate that δ-TT exerts its antitumor activity by targeting the CSC subpopulation of A375 melanoma cells and might represent a novel chemopreventive/therapeutic strategy against melanoma.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol

Marzagalli

Moretti

Messi

et al. 2018

Sci Rep

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“…The discovery of pathways essential for modulating stemness properties has contributed to the identification of several molecules that could eliminate GSCs, including new antineoplastic agents from natural sources [106][107][108][109][110][111][112][113]. A summary of current potential treatments is presented in Table 1 and Fig.…”

Section: Current Strategies Targeting Cancer Stem Cellsmentioning

confidence: 99%

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

et al. 2021

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Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15–18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.

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“…Recent evidence has shown that cancer stem cells undergo continuous mutations and are responsible for drug resistance and relapse. Targeting cancer stem cells is challenging, but identifying drugs which can work on stem cells can solve the relapse and resistance seen in most of the high-grade tumors [7].…”

Section: Introductionmentioning

confidence: 99%

Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines

Koroth

Nirgude

Tiwari

et al. 2019

BMC Complement Altern Med

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Background Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. Methods Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. Results Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). Conclusion Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.

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Anti-Cancer Phytometabolites Targeting Cancer Stem Cells

Cited by 29 publications

References 228 publications

Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol

Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol

Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines

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