Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate

Weiyu Chen; Lingyun Xu; Edwin Chang; Gayatri Gowrishankar; Katherine W Ferrara; Sanjiv Sam Gambhir

doi:10.1186/s12906-022-03541-0

Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate

BMC Complement Med Ther. 2022 Mar 7;22(1):58. doi: 10.1186/s12906-022-03541-0.

Authors

Weiyu Chen^{1

2

3}, Lingyun Xu^{4

5}, Edwin Chang^{4

5}, Gayatri Gowrishankar^{4

6}, Katherine W Ferrara^{7

8

9}, Sanjiv Sam Gambhir^{4

6

5

10

11

12}

Affiliations

¹ Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA. weiyuchen@zju.edu.cn.
² Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA. weiyuchen@zju.edu.cn.
³ The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, Zhejiang, China. weiyuchen@zju.edu.cn.
⁴ Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA. kwferrar@stanford.edu.
⁸ Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA. kwferrar@stanford.edu.
⁹ Bio-X Program at Stanford, Stanford University, Stanford, CA, USA. kwferrar@stanford.edu.
¹⁰ Bio-X Program at Stanford, Stanford University, Stanford, CA, USA.
¹¹ Department of Bioengineering, Stanford University, Stanford, CA, USA.
¹² Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.

Abstract

Background: Gastric signet ring cell carcinoma (SRCC) is an aggressive gastric adenocarcinoma with a poor prognosis when diagnosed at an advanced stage. As alternative medicine, two natural supplements (ascorbate (AA) and sodium alpha lipoate (LA)) have been shown to inhibit various cancers with mild side effects.

Methods: These two natural supplements and a series of combinations (AA&LA, AA+LA and LA + AA) were incubated with non-SRCC cells (GPM-1), patient-derived gastric origin SRCC (GPM-2), gastric-origin SRCCs (HSC-39 and KATO-3), human pancreatic (MIA PaCa-2) and ovarian (SKOV-3) cells for evaluating their therapeutic effects. Moreover, these treatments were applied in 3D-cultured organoids to reveal the feasibility of these approaches for in vivo study.

Results: Analyzing their antioxidant capabilities and dose-response curves, we observed that all four gastric cell lines, including three patient-derived cell lines were sensitive to ascorbate (~ 10 mM). The influence of ascorbate incubation time was studied, with a 16-h incubation found to be optimal for in vitro studies. Moreover, a simultaneous combination of AA and LA (AA&LA) did not significantly inhibit cell proliferation, while prior LA treatment increased the growth inhibition of AA therapy (LA + AA). Anti-cancer efficacy of AA was further confirmed in 3D-cultured SRCC (KATO-3) organoids.

Conclusions: This study highlights the potential of AA and LA + AA in treating gastric origin SRCC, and demonstrates the influence of order in which the drugs are administered.

Keywords: Ascorbate; Gastric signet ring cell carcinoma; Natural supplements; Organoid; Sodium alpha lipoate.

MeSH terms

Adenocarcinoma*
Carcinoma, Signet Ring Cell* / drug therapy
Carcinoma, Signet Ring Cell* / pathology
Complementary Therapies*
Humans
Sodium
Stomach Neoplasms* / drug therapy
Stomach Neoplasms* / pathology

Substances

Sodium