2. Academic Validation
  3. Isolation and anticancer activity evaluation of rare Bisaryl anthraquinone antibiotics from novel Streptomyces sp. strain of NW Himalayan region

Isolation and anticancer activity evaluation of rare Bisaryl anthraquinone antibiotics from novel Streptomyces sp. strain of NW Himalayan region

  • Chem Biol Interact. 2022 Sep 25;365:110093. doi: 10.1016/j.cbi.2022.110093.
Ravi Singh Manhas 1,  Syed Mudabir Ahmad 2,  Khalid Bashir Mir 2,  Ajaz Ahmed 3,  Snigdha Sharma 4,  Diksha Manhas 5,  Harshita Tiwari 3,  Amit Kumar 6,  Amit Nargotra 3,  Utpal Nandi 5,  Debaraj Mukherjee 7,  Anindya Goswami 8,  Asha Chaubey 9
Affiliations

Affiliations

  • 1 Fermentation & Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India.
  • 2 Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India.
  • 3 Natural Products & Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India.
  • 4 Fermentation & Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
  • 5 PK-PD Toxicology Division, CSIR- Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India.
  • 6 Quality Management & Instrumentation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
  • 7 Natural Products & Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India. Electronic address: [email protected].
  • 8 Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India. Electronic address: [email protected].
  • 9 Fermentation & Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research, CSIR-Human Resource Development Centre, Campus Ghaziabad, 201002, India. Electronic address: [email protected].
PMID: 35985519 DOI: 10.1016/j.cbi.2022.110093
Abstract

Biosynthesis of bisaryl preanthraquinone Antibiotics by various Microorganisms differs in monomeric subunits as well as their dimerization positions leading to different configurations. The present study relates to the production of rare bisaryl anthraquinone Antibiotics by a new Streptomyces strain isolated from Shivalik region of NW Himalayas. In vitro Anticancer and anti-migratory effects of Setomimycin (9,9' bisanthraquinone Antibiotic) was seen with a significant reduction in the expression of both MEK as well as ERK pathways in a dose dependent manner at 6.5 μM & 8 μM concentration in HCT-116 and 5.5 μM & 7 μM concentration in MCF-7 cells. In vivo studies in aggressive orthotopic mouse mammary carcinoma model (4T1) demonstrated about 76% reduction of primary tumor weight and 90.5% reduction in the tumor volume within two weeks. In vivo pharmacokinetics study of setomimycin revealed that it can be rapidly absorbed with an adequate plasma exposure and half-life which can be linked to its in vivo efficacy.

Keywords

4T1; Apoptosis; Bcl-2; Bisaryl athraquinone; Invasion; MEK; NW Himalayas; Setomimycin; Streptomyces sp..

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