Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study

Firli Rahmah Primula Dewi; Sephia Tiara Marviella; Sri Puji Astuti Wahyuningsih; A'liyatur Rosyidah; Vuanghao Lim; Lionel Lian Aun In; Amy Yi Hsan Saik; Bimaji Ariyogo; Mee Lee Looi

doi:10.55730/1300-0152.2704

Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study

Turk J Biol. 2024 Sep 17;48(5):279-289. doi: 10.55730/1300-0152.2704. eCollection 2024.

Authors

Firli Rahmah Primula Dewi¹, Sephia Tiara Marviella¹, Sri Puji Astuti Wahyuningsih¹, A'liyatur Rosyidah², Vuanghao Lim³, Lionel Lian Aun In⁴, Amy Yi Hsan Saik⁵, Bimaji Ariyogo¹, Mee Lee Looi⁶

Affiliations

¹ Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.
² Research Center for Vaccine and Drug, National Research and Innovation Agency, Bogor, Indonesia.
³ Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
⁴ Department of Biotechnology, Faculty of Applied Sciences, University College Sedaya International, Kuala Lumpur, Malaysia.
⁵ Department of Pre-Clinical Sciences, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Malaysia.
⁶ Learning Planning and Development, Centre for Future Learning, Taylor's University, Malaysia.

Abstract

Background/aim: Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU).

Materials and methods: This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ). To induce colon cancer in rats, MNU (10 mg/Kg BW) was administrated intrarectally three times per week for four weeks. The treatment of Q (40 mg/Kg BW) or NDQ (40 mg/Kg BW) was given intraperitoneally twice a week for 6 weeks. Cancer progression of all cohorts was evaluated by performing body and colon weight measurements, which involved the following: ELISA assay-specific to metastatic marker matrix metalloprotein-9 (MMP-9), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 α (HIF1α), vascular endothelial growth factor, protein 53 (p53) and immunohistochemistry staining of Caspase-3 and Ki-67 proteins. Observation of cancer metastasis to the lung was also performed.

Results: NDQ significantly inhibited cancer aggressiveness by causing an increment in body weight gain and the growth rate-while reducing the colon weight compared to the K- group. Moreover, decreased levels of MMP-9, CEA, HIF-1α, and Ki67 and increased levels of p53 and Caspase-3 were more significant in the NDQ group than in the Q group. The lung tumor metastases in the NDQ group were fewer than in the K- group.

Conclusion: NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

Keywords: Anticancer; colon cancer; metastasis; nanodiamond; quercetin.

Grants and funding

This work was supported by the Riset dan Inovasi untuk Indonesia Maju (RIIM), (National Research and Innovation Agency (BRIN) under Grant no. B-1810/III.1/FR/11/2022.