L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells

Jung, Soo A.; Lee, Dong Hoon; Moon, Jung Hwan; Hong, Seung Woo; Shin, Ji Sun; Hwang, Ih Yeon; Shin, Yong-June; Kim, Jeong Hee; Gong, Eun Yeung; Kim, Seung Mi; Lee, Eun Young; Lee, Seul; Kim, Jeong Eun; Kim, Kyu Pyo; Hong, Yong Sang; Lee, Jung Shin; Jin, Dong Hoon; Kim, Tae Won; Lee, Wang Jae

doi:10.1016/j.freeradbiomed.2016.03.009

Cited by 39 publications

(35 citation statements)

References 22 publications

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“…In our previous study, SVCT-2-independent colon cancer cells (e.g., HCT116, HCT8) but not SVCT-2-dependent colon cancer cells (e.g., DLD-1, SW480, and SW620) showed resistance to vitamin C (Jung et al, 2016). HCT116 is a SVCT-2 independent p53 colon cancer cell line, which showed the anti-cancer effect upon sulindac and vitamin C treatment.…”

Section: Discussionmentioning

confidence: 93%

“…Moreover, we recently identified that the combination therapy of vitamin C with cetuximab, an antibody directed against the epithermal growth factor receptor, rescues the cetuximab resistance in KRAS mt/SVCT-2 dependent colon cancer cells (Jung et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we investigate the anti-cancer effects upon combination treatment with sulindac and vitamin C using HCT116 colorectal cancer cell line, which is a representative colon cancer cell line to examine roles of p53 in several studies (Enge et al, 2009;Funauchi et al, 2015;Galligan et al, 2005) and SVCT-2 independent cell line (Jung et al, 2016). Here, we report that combination therapy can synergistically induce apoptosis in the HCT116 in a p53-and ROS-dependent manner.…”

Section: Introductionmentioning

confidence: 97%

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Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells

et al. 2016

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells

et al. 2016

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“…Here, KRAS-mutant colorectal cancer cells in culture preferentially took up DHA rather than ascorbate and were selectively sensitive to and killed by DHA (25). Yet, in a different study using a range of KRAS-mutant colorectal cell lines, ascorbate transport, and sensitivity was reliant on SVCT2, not GLUTs (27). Due to very low or undetectable physiological DHA concentrations in plasma (<10% of total ascorbate) (28, 29), its uptake is likely to be of minor importance in vivo , and DHA transport is therefore not discussed further in this review.…”

Section: Ascorbate Transport and Eliminationmentioning

confidence: 99%

“…SVCT2 expression sensitized KRAS-mutant human colon cancer cells to combined administration of ascorbate and cetuximab in vitro (27). Combination treatment also reduced tumor growth in KRAS-mutant xenograft tumors dependent on SVCT2 levels; intracellular or tumor ascorbate levels have again not been measured (27).…”

Section: Sodium-dependent Vitamin C Transportermentioning

confidence: 99%

Vitamin C Transporters in Cancer: Current Understanding and Gaps in Knowledge

2017

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Sufficient uptake and whole body distribution of vitamin C (ascorbate) is essential for many biochemical processes, including some that are vital for tumor growth and spread. Uptake of ascorbate into cancer cells is modulated by availability, tumor blood flow, tissue diffusion parameters, and ascorbate transport proteins. Uptake into cells is mediated by two families of transport proteins, namely, the solute carrier gene family 23, consisting of sodium-dependent vitamin C transporters (SVCTs) 1 and 2, and the SLC2 family of glucose transporters (GLUTs). GLUTs transport the oxidized form of the vitamin, dehydroascorbate (DHA), which is present at negligible to low physiological levels. SVCT1 and 2 are capable of accumulating ascorbate against a concentration gradient from micromolar concentrations outside to millimolar levels inside of cells. Investigating the expression and regulation of SVCTs in cancer has only recently started to be included in studies focused on the role of ascorbate in tumor formation, progression, and response to therapy. This review gives an overview of the current, limited knowledge of ascorbate transport across membranes, as well as tissue distribution, gene expression, and the relevance of SVCTs in cancer. As tumor ascorbate accumulation may play a role in the anticancer activity of high dose ascorbate treatment, further research into ascorbate transport in cancer tissue is vital.

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Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2

Jang

Kim

Hong

et al. 2023

Cell Biochemistry & Function

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Curcumin is a natural polyphenol that is extracted from the rhizomes of the turmeric plant (Curcuma longa), a member of the ginger family. It has been used for centuries in traditional Indian and Chinese medicine for its medicinal properties, including anti‐inflammatory, antioxidant and antitumor effects. SVCT2 (Solute Carrier Family 23 Member 2, also known as SLC23A2) is a protein that plays a role in the transport of Vitamin C (Ascorbic Acid) into cells. SVCT2 plays an important role in tumor progression and metastasis, however, the molecular mechanisms of curcumin on SVCT2 have not been studied to date. Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner. We found that curcumin reduced the expression of SVCT2 in cancer cells with a wild type p53, but not in those with a mutant type of p53. SVCT2 downregulation also reduced the MMP2 activity. Taken together, our results indicate that curcumin inhibited human cancer cell growth and migration by regulating SVCT2 through a downregulating p53. These findings provide new insights into the molecular mechanisms of curcumin's anticancer effects and potential therapeutic strategies for the treatment of metastatic migration.

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L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells

Cited by 39 publications

References 22 publications

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells

Vitamin C Transporters in Cancer: Current Understanding and Gaps in Knowledge

Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2

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