Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3

Gu, Yue-Yu; Chen, Menghua; May, Brian H.; Liao, Xiao‐Zhong; Liu, Jiahui; Tao, Lan-Ting; Sze, Daniel Man-Yuen; Zhang, Anthony Lin; Mo, Sui-Lin

doi:10.1016/j.phymed.2018.10.004

Cited by 51 publications

(25 citation statements)

References 28 publications

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“…In the same way, the induction of apoptosis by natural compounds may have been orchestrated by mediating proteins such as Bax and Bcl-2 and caspase-3, as well as by the processes of cell cycle arrest [23]. We have also shown that the cell apoptosis induction is occurring in response to various stress conditions and it includes the regulation of the p21 gene, which is one of the major tumor suppressor p53 targets, a dependent p21 nuclear translocation that could promote cell survival and inhibits CDK2 preventing cell cycle progression [24].…”

Section: Discussionmentioning

confidence: 99%

A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro

et al. 2020

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Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.

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Section: Discussionmentioning

confidence: 99%

A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro

et al. 2020

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“…However, the cytotoxicity and mechanism of the styryllactone compounds, first isolated in our laboratory, have not been studied in SMMC-7721, HepG2, SW1116 and SGC-7901 cell lines. Besides, SMMC-7721 cells (Kim, 2009), HepG2 cells (Li et al, 2019), SW1116 cells (Gu et al, 2018) and SGC-7901 (Wang et al, 2018) were all reported to be studied in apoptosis-induced research via activaing caspase proteas, indicating that they were able to be used in our mechanism research. As a result, to evaluate whether the styryllactones isolated could resulte in cytotoxicity and apoptosis via caspase-3, -8 and -9 activation, these four human cell lines were choosen in our research.…”

Section: Discussionmentioning

confidence: 99%

Hydroxypropyl-β-Cyclodextrin Complexes of Styryllactones Enhance the Anti-Tumor Effect in SW1116 Cell Line

Chen

et al. 2020

Front. Pharmacol.

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Styryllactones, a class of compounds obtained from the genus Goniothalamus (Annonaceae), have demonstrated in vitro antitumor activity. However, the aqueous solubility of these compounds is poor. In this study, we identified the absolute configurations of the previously isolated compounds, which were first isolated in our laboratory, by single-crystal X-ray diffraction analysis using Cu Ka radiation. Subsequently, the antitumor activities of the compounds were evaluated by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining in four tumor cell lines. The induced apoptosis activity of leiocarpin E-7ʹ-Monoacetate was studied by an annexin V fluorescein isothiocyanate/propidium iodide double-staining experiment, and the caspase activity was tested in the SW1116 cell line. The results demonstrated that the antitumor activities of cheliensisin A and goniodiol-7-monoacetate were limited by their poor water solubility. To address this issue, hydroxypropyl-b-cyclodextrin (HP-b-CD) complexes of the compounds were synthesized by the saturated aqueous method. The complexes were then analyzed using a differential scanning calorimeter. The IC 50 of cheliensisin A was reduced by 45% and 58% against SW1116 and SMMC-7721 cell lines, respectively. Similarly, the IC 50 of goniodiol-7-monoacetate was reduced by 55% and 34% against the two tumor cell lines, respectively. To further evaluate whether the styryllactones and complexes possessed selectivity against cancer cell lines and normal cell lines, toxicity against human normal cell line (HEK293T) was evaluated. The results demonstrated that the HP-b-CD complexes displayed more cytotoxicity than the respective pristine compounds against the HEK293T cell line. However, there existed a therapeutic window when the complexes were applied against cancer cell lines. In summary, the synthesis of several styryllactone compounds complexed with HP-b-CD was reported for the first time. These complexes could significantly enhance the cytotoxic effects of styryllactone compounds.

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“…Besides, Bcl-2 family has a delicate balancing effect on apoptosis and tumorigenesis [25]. Gu et al, suggested that the induction of apoptosis in CRC cells was a molecular mechanism through the effects on Bcl-2, Bax and Caspase3 [26]. IGFs include IGF-I, IGF-II, relevant receptors IGF-IR and IGF-IIR, and IGF-binding proteins (IGFBPs), all of which exert crucial roles in anti-apoptosis and facilitating cell proliferation [27,28].…”

Section: Discussionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.

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Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3

Cited by 51 publications

References 28 publications

A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro

A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro

Hydroxypropyl-β-Cyclodextrin Complexes of Styryllactones Enhance the Anti-Tumor Effect in SW1116 Cell Line

HSPA4 knockdown retarded progression and development of colorectal cancer

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